The purpose of this work is to understand how the retinal pigment epithelium degrades the photoreceptor cell outer segments. Cathepsin D, a proteinase, and phospholipases A1 and A2 are primarily responsible for degrading the outer segments. The projects and experimental approaches currently underway and planned include (1) characterization of the proteolysis of opsin, the vertebrate photopigment, by cathepsin D; (2) the role of membrane fluidity in allowing cathepsin D access to its principal substrate, opsin; (3) testing the levels of lysosomal hydrolases present in the retinal pigment epithelium and other phagocytic cells in a strain of rats (RCS) afflicted with an hereditary retinal degeneration known to be caused by failure of the retinal pigment epithelium to phagocytize the photoreceptor cells which have been shed.